US2007088164A1PendingUtilityA1

Combinatorial library approach to iminocyclitols with biological activity

Individually held — no corporate assignee on recordPriority: Sep 2, 2005Filed: Sep 1, 2006Published: Apr 19, 2007

Est. expirySep 2, 2025(expired)· nominal 20-yr term from priority

Inventors:Robert Moriarity Carmen Mitan Kenneth R. Phares

C07D 211/74C07D 491/04C07D 493/04C07D 207/12

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Claims

Abstract

A method of synthesizing stereochemically defined iminocyclitol comprises replacing an intraring oxygen in a cyclic sugar by an intraring imine to form an iminocyclitol, wherein said iminocyclitol has a defined stereochemical configuration different from a stereochemical configuration of the cyclic sugar. The invention also provides combinatorial libraries of iminocyclitol compounds, allowing for diverse C1 and N-substitution. In addition, provided are methods of treating viral infections with iminocyclitols compounds.

Claims

exact text as granted — not AI-modified

1 . A method of synthesizing stereochemically defined iminocyclitol comprising
replacing an intraring oxygen in a cyclic sugar by an intraring imine to form an iminocyclitol, wherein said iminocyclitol has a defined stereochemical configuration different from a stereochemical configuration of the cyclic sugar.

2 . The method of claim 1 , wherein said replacing an intraring oxygen comprises reacting the cyclic sugar with a reagent comprising NH 3 .

3 . The method of claim 1 , wherein the cyclic sugar is an aldopentose in a 4-deoxy 1,4 furanose form, an aldohexose in a 4-deoxy 1,4 furanose form or an aldohexose in a 2,5-dideoxy pyranose form and wherein the cyclic sugar is substituted at the C1 position by R 1 , wherein R 1 is an alkyl group comprising from 1 to 20 carbon atoms.

4 . The method of claim 3 , further comprising reacting a protected lactone compound with a Grignard reagent R 1 MgX to form the cyclic sugar, wherein a stereochemical configuration of the protected lactone compound is the same as the stereochemical configuration of the cyclic sugar.

5 . The method of claim 4 , further comprising protecting hydroxyl groups of an unprotected lactone compound to form the protected lactone compound, wherein a stereochemical configuration of the unprotected lactone compound is the same as the stereochemical configuration of the protected lactone compound.

6 . The method of claim 5 , wherein the unprotected lactone compound is an aldopentose or an aldohexose in a 4-deoxy 1,4 furanose form and wherein said protecting hydroxyl groups comprises protecting a hydroxyl group on the C5 atom of the unprotected lactone compound with methanesulfonate, tosylate or triflate protective group.

7 . The method of claim 5 , wherein the unprotected lactone compound is an aldohexose in a 4-deoxy 1,4 furanose form and wherein said protecting hydroxyl groups comprises protecting a hydroxyl group on the C6 atom of the unprotected lactone compound with a trityl or t-butyldimethylsiloxy group.

8 . The method of claim 5 , wherein the unprotected lactone compound is an aldohexose in a 2,5-dideoxy pyranose form and wherein said protecting hydroxyl groups comprises protecting a hydroxyl group on the C6 atom of the unprotected lactone compound with a methanesulfonate protective group.

9 . The method of claim 5 , wherein the unprotected lactone compound an aldopentose or an aldohexose in a 4-deoxy 1,4 furanose and wherein said protecting hydroxyl groups comprises protecting a hydroxyl group on the C2 atom and a hydroxyl group on the C3 atom by an isopropyldene.

10 . The method of claim 5 , wherein the unprotected lactone compound is an aldohexose in a 2,5-dideoxy pyranose form and wherein said protecting hydroxyl groups comprises protecting a hydroxyl group on the C3 atom and a hydroxyl group on the C4 atom by an isopropyldene.

11 . The method of claim 5 , wherein the unprotected lactone compound is an aldopentose or an aldohexose in a 4-deoxy 1,4 furanose, wherein said protecting hydroxyl groups comprises protecting a hydroxyl group on the C2 atom and a hydroxyl group on the C3 atom by benzyl, t-butyldimethylsiloxy or triphenyl groups.

12 . The method of claim 5 , wherein the unprotected lactone compound is an aldohexose in a 2,5-dideoxy pyranose form and wherein said protecting hydroxyl groups comprises protecting a hydroxyl group on the C3 atom and a hydroxyl group on the C4 atom by benzyl, t-butyldimethylsiloxy or triphenyl groups.

13 . The method of claim 1 , further comprising hydrogenating the iminocyclitol to form a hydrogenated iminocyclitol, wherein a stereochemical configuration of the hydrogenated iminocyclitol is the same as the stereochemical configuration of the iminocyclitol.

14 . The method of claim 13 , wherein hydrogenating the iminocyclitol is carried out in the presence of a catalyst.

15 . The method of claim 14 , wherein the catalyst comprises Pd/C and acetic acid.

16 . The method of claim 13 , further comprising aminating the hydrogenated iminocyclitol to form a N-alkyl-C-alkyl iminocyclitol, wherein a stereochemical configuration of the N-alkyl-C-alkyl iminocyclitol is the same as the stereochemical configuration of the hydrogenated iminocyclitol.

17 . The method of claim 16 , wherein aminating the hydrogenated iminocyclitol comprises reacting the hydrogenated iminocyclitol with an aldehyde R 2 CHO and the N atom of the N-alkyl-C-alkyl has a substituent group R 2 CH 2 , and wherein R 2 is hydrogen or an alkyl group comprising from 1 to 20 carbon atoms, and deprotecting C2 and C3 hydroxyl groups of the N-alkyl-C-alkyl iminocyclitol.

18 . The method of claim 16 , wherein hydrogenating the iminocyclitol, reacting the hydrogenated iminocyclitol with an aldehyde and deprotecting C2 and C3 hydroxyl groups of the N-alkyl-C-alkyl iminocyclitol are carried out simultaneously.

19 . A stereochemically defined iminocyclitol compound or a salt thereof, wherein said compound having a formula selected from the group consisting of

R 1 is an alkyl group comprising from 1 to 20 carbon atoms,
R 2 is hydrogen or an alkyl group comprising from 1 to 20 carbon atoms,
R 3 is hydrogen or an alkyl group comprising from 1 to 20 carbon atoms,
R 4 is hydrogen or a first protecting group,
R 5 is hydrogen or a second protecting group,
R 6 is hydrogen or a third protecting group selected from the group consisting of methanesulfonate, tosylate and triflate;
R 7 is hydrogen or a fourth protective group selected from the group consisting of t-butyldimethylsiloxy and tretyl radicals, wherein the first and the second protective form together isopropylidene or cyclohexylidene or are identical protective groups selected from the group consisting of benzyl, t-butyldimethylsiloxy radical and triphenylmethyl.

20 . The compound of claim 19 or a salt thereof, wherein a stereochemical configuration of the formula of the compound is

and wherein R 1 , R 2 and R 6 are as defined in claim 19 .

21 . The compound of claim 19 or a salt thereof, wherein a stereochemical configuration of the formula is

and wherein R 1 , R 2 and R 6 are as defined in claim 19 .

22 . The compound of claim 19 or a salt thereof, wherein a stereochemical configuration of the formula of the compound is